London and South East

Our research in London and the South East spans all the major types of blood cancer. We are supporting research that is revealing how blood cancer works, driving smarter and faster diagnosis, and finding new treatments and care.

We also have Trials Acceleration Programme (TAP) centres in London and Oxford, and an additional affiliate centres in London and Cambridge. These centres are part of a network that are helping to speed up blood cancer clinical trials so we can deliver new treatments to people with blood cancer in the fastest possible way.

Guys and St Thomas’ NHS Foundation Trust

We have a Trials Acceleration Programme (TAP) centre based at the Guys and St Thomas’ NHS Foundation Trust.

Two TAP trials are being led by Professor Claire Harrison who is based at this centre, which are looking at new ways to treat people with myeloproliferative neoplasms (MPN).

The MAJIC clinical trial is looking at using ruxolitinib to treat people who are unable to tolerate standard therapy. And the Tamarin study wants to find out if a drug that is already used to treat breast cancer can help people who have JAK2 and CALR gene changes that are commonly found in MPN.

Imperial College London

Research at Imperial College London has a focus on finding new treatments for multiple myeloma and we are testing a new and exciting CAR-T therapy for lymphoma. We are also developing new ways to treat AML, and we are finding out what genetic changes happens in cells that allow them to ignore the warning signs of DNA damage, which can lead to cancer.

Professor Guido Franzoso and his team have developed a new cancer drug which they plan to trial in people with multiple myeloma. But the drug called DTP3 could actually be used to treat other types of blood cancer, including lymphoma. The team plan to test DTP3 in the lab to see if it is effective at killing lymphoma cells, and to see if there are any toxic effects. If this is successful, they plan to start a new trial of DTP3 in people with lymphoma who are unable to tolerate standard treatments, such as chemotherapy and radiotherapy.

One of our other myeloma projects is being led by Professor Anastasios Karadimitris. The team want to identify the genes, that although are not mutated, they are important for myeloma cell growth and survival. They also want to investigate how a group of proteins called BET drive bone destruction in myeloma, and if drugs that inhibit these proteins might help to prevent bone damage. Taken together this research hopes to provide new insights into what sustains the growth of myeloma cells and will reveal new treatment targets.

Immunotherapy is a type of treatment that can direct a population of immune cells that normally recognise infectious agents, such as bacteria, to recognise cancer cells and kill them. These cells are called cytotoxic T-cells. But leukaemia can fight back by recruiting a set of T-cells called ‘regulatory T-cells’, which are able to block the killer immune cells. Dr Cristina Lo Celso and her team are using powerful microscopy to analyse the evolving interactions between acute myeloid leukaemia cells and T cells as the disease develops. Once they understand these processes, the researchers can exploit the immune cells to win the fight against leukaemia.

An oncogene is a normal gene, but it has the potential to cause cancer. Accidental activation of oncogenes occurs regularly in healthy cells without causing cancer. This is because healthy cells sense the presence of cancer genes as they lead to significant changes in the cell known as ‘cancer stress’. As a response to cancer stress, healthy cells undergo suicide or stop dividing, which generally prevents the cell entering a cancerous state. Unfortunately, some cells pass this safety barrier leading to leukaemia and lymphoma. Dr Niklas Feldhahn wants to understand what genetic changes happen in the cells that allow them to ignore the warning signs of cancer stress, and will explore ways of reversing this.

One of the most exciting avenues in cancer research at the moment is CAR-T therapy. This is where immune cells called T-cells are engineered with genes called chimeric antigen receptors (CAR), so they can target selectively molecules that are found on the surface of cancer cells. Once the modified T-cell binds to the surface of the cancer cell, a signal is sent to the body’s immune system to destroy the marked cell. Professor Anastasios Karadimitris is modifying T-cells to target a molecule called CD19, which is found on the surface of B-cell lymphomas. If successful, this could be a promising targeted treatment for people with lymphoma.

King's College London

Research at King’s College London is mainly centred round AML. As well as searching for new treatments; we want to help those who are at risk of their disease returning. And we funding a project that wants to individualise treatments for people with acute promyelocytic leukaemia (APL) – a rare type of AML. We have an exciting programme of myelodysplastic syndrome (MDS) research that aims to find out why some cases develop into more aggressive diseases like AML, and we also want to find new ways to treat the disease.

Boosting the effectiveness of Graft versus Host Disease (GVHD) treatment and exploring ways to treat people with early stage CLL are also a focus.

Some people with AML can be cured with intensive chemotherapy, but others will unfortunately see their cancer return. We still don’t fully understand why some people do well, and others do not. Along with other researchers, Dr Richard Dillon has now developed a simple blood test that can detect trace levels of leukaemia cells after chemotherapy. The test is able to detect the mutated NPM1 gene, which is found in around a third of all cases of AML. Doctors can now accurately predict who is at risk of relapsing, so they can tailor their treatment accordingly. Because of its success, the test has quickly moved to the pathology services at King’s, and is now available to people with AML across the UK. This means on a weekly basis, people who are doing well on their chemotherapy are being identified, and some are even avoiding having a bone marrow transplant procedure altogether. Dr Dillon now wants to detect cells in the bone marrow that might be able to lie dormant and resist chemotherapy, causing relapse.

We are also supporting a research project that wants to understand what causes leukaemia to develop, which could lead to much needed newer treatments for AML. Abnormal gene expression is a common feature in leukaemia, and emerging evidence shows that proteins called histone modification enzymes play a key role in this process. Professor Eric So aims to define the role of individual histone modification enzymes in the development of leukaemia, with a focus on AML. This could lead to the development of more effective but less toxic leukaemia therapies.

Acute promyelocytic leukaemia (APL) is a rare form of AML. APL happens when parts of two chromosomes (chromosomes 15 and 17) swap over to create a ‘fusion gene’ called PML/RARA. The fusion gene generates an abnormal protein called PML-RARα, which triggers cells to grow out of control and cause APL. People with APL are usually given a drug that targets the PML-RARα protein alongside chemotherapy. Although this initial treatment can cure many people, unfortunately, others relapse or go on to develop a different type of leukaemia. Professor Ellen Solomon and her team are looking at the interactions between the PML-RARα protein and the bone marrow cells to see if this explains why we see such a varied treatment response in APL.

We are also supporting research which is looking at how a type of blood cancer called myelodysplastic syndrome (MDS) develops, and why some people with MDS go on to develop AML. Professor Ghulam Mufti wants to investigate if autoimmunity – where the immune system attacks its own cells – helps to prevent MDS progressing to AML. This could pave the way for future treatment approaches. In another project, Dr Mufti is looking closely at the immune cells of people with MDS, which could shed some light on how the disease progresses. Taken together, this programme of research could not only reveal how and why some MDS cases develop into more aggressive diseases like AML, but may also open up a new avenue of treating MDS by manipulating the immune environment.

As well as finding new ways to treat people with AML, we are also supporting research that aims to prevent the disease returning after stem cell transplants. Preventing relapse after chemotherapy or stem cell transplants is really important because AML can be harder to treat when this happens. Dr Victoria Potter is leading the PRO-DLI trial, which wants to see if giving white blood cells from the stem cell transplant donor can be used after transplantation to prevent relapse. And Professor Farzin Farzaneh is looking at using immunotherapy to boost

the killing ability of the body’s immune system so it can fight back against leukaemia. He is developing two new treatments that will be given when AML is in remission to prevent relapse.

Graft versus host disease (GVHD) is a complication that can happen after a stem cell transplant from another person. It happens when the white blood cells in the donated stem cells or bone marrow attack the recipient’s cells in the body. During the last few years, Professor Francesco Dazzi and his team of researchers have developed a way to treat severe GvHD with mesenchymal stromal cells (MSC). In order to maximise the effects of this treatment, Professor Dazzi will be studying how MSCs work in people with GvHD, and select those who are more likely to respond to MSC treatment. Researchers also plan to explore ways to boost the effectiveness of MSC treatment.

We are supporting one project that is looking for ways to slow down the progression of chronic lymphocytic leukaemia (CLL). Professor Stephen Devereux has been leading one of our TAP trials called CyCLLe. He wants to see if cyclosporin A can affect the rate at which leukaemia cells grow, and if this could be an effective treatment for people with early CLL. Cyclosporin A has been used for many years to reduce the activity of the immune system in people who have autoimmune diseases or who have received organ transplants. Researchers think that healthy immune cells may help CLL to grow, so cyclosporin A could dampen down their activity and slow the rate at which leukaemia cells grow. If successful, this treatment could slow down the disease in its early stages, so we can prevent progression and the need for strong drugs.

Queen Mary University of London

We are supporting research at Queen Mary University of London that is looking at ways to prevent treatment relapse in acute lymphoblastic leukaemia (ALL). We also have a project that assessing a potential new drug treatment in blood cancers that affect B cells, such as diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukaemia (CLL). And we are looking at ways to improve the way we manage people who have rarer forms of myelodysplastic syndrome (MDS) that are inherited.

Although lots of people with ALL respond to initial treatment, many will unfortunately relapse. ALL can return after treatment through a variety of ways. One mechanism is down to a small population of ‘sleeping’ leukaemic cells, which can resist chemotherapy treatment and cause late cancer recurrence. Dr Bela Wrench wants to find ways to target these sleeping leukaemic cells, which could help prevent ALL from returning.

We are also supporting a project that is looking at a possible new treatment target for blood cancers that affect B cells, such as DLBCL and CLL. Despite some great advances in research, our knowledge of how these cancers grow is still rather limited, and there is a continuing need for new treatments. Dr Melania Capasso has found a newly identified protein called HVCN1, which is found on CLL and DLBCL cells and on normal B cells. She now wants to fully characterise the protein’s function, and to see if she can target it with new drugs.

Although the majority of MDS and AML cases are thought to result from genetic mistakes picked up over a person’s lifetime, there are some rare cases of inherited genetic faults that increase the likelihood of a cancer developing. Professor Inderjeet Dokal is studying people with inherited MDS, so we can improve the management of this group of people.

UCL Great Ormond Street Institute of Child Health

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University College London

Research at The University College London (UCL) is looking for new treatments for acute lymphoblastic leukaemia (ALL), lymphoma and acute myeloid leukaemia (AML). We have an ambitious project that could transform the way we treat childhood ALL. We are also finding out what causes chemotherapy resistance in ALL and what we can do to overcome this. And we are running three clinical trials – one is a Trials Acceleration Programme (TAP) trial that is testing a new treatment for relapsed myeloma, and the others want to reduce the side effects of treatments - chemotherapy in Burkitt lymphoma and radiotherapy in children and adolescents with Hodgkin lymphoma. We also have a project that wants to increase the effectiveness of mini transplants – where people receive a stem or bone marrow transplant from a sibling.

People with ALL are usually treated with chemotherapy, which works by destroying cells that are in the process of dividing. Because cancer cells divide much more often than most normal cells, chemotherapy is much more likely to kill them. But chemotherapy often damages healthy cells in the body too. This can leave people with long-term health issues such as heart disease and strokes, infections, fertility problems, and tragically, even the increased risk of a second cancer appearing later on in life. And if ALL returns after chemotherapy, it becomes difficult to treat. Part of our research that we are funding at UCL is developing better and less harmful treatments for people with ALL.

One promising treatment approach is to use ‘oncolytic virus therapy’ to treat cancer, which is a more targeted approach than chemotherapy. We are supporting a project being led by Professor Fielding, who is engineering the measles virus to seek out and destroy ALL cells, leaving healthy cells unharmed.

Our research is also looking at why leukaemia can become resistant to treatment, and what causes it to return. Leukaemia can often stop responding to treatment because some of the cancer cells develop new genetic faults that help them survive and grow, potentially leading to a hard-to-treat cancer coming back. Researchers also know that there are a small population of ‘sleeping’ leukaemic cells, which can resist chemotherapy treatment because they are not dividing rapidly. These dormant leukaemic cells can wake up after treatment and cause the leukaemia to return.

Dr Marc Mansour is looking at chemotherapy resistance in a particular subtype of ALL called T-ALL, which affects T cells. The team are focusing on a gene called EZH2, which normally silences many other genes in T cells, and can become lost or mutated in T-ALL. When this happens, the genes that are usually silenced by EZH2 become continuously switched on. Dr Mansour and his team will test drugs in the lab to find those that selectively kill cells that are missing the EZH2 gene. Researchers hope they can develop drugs that are targeted to leukaemia cells in people with high risk T-cell ALL, that will have fewer side effects than current chemotherapies.

Professor Tariq Enver and his team are leading a project that has the potential to revolutionise the way we treat children with ALL. They are building up a comprehensive picture of how ALL progresses over time, which will contribute to the development of new drugs that target the specific characteristics of ALL cells, so that healthy tissues can be spared. This will be a huge step forwards from the traditional chemotherapy drugs that are usually given to children and young adults, which can cause devestating life-changing side effects.

One of our research programmes is using a type of immunotherapy called T cell receptor (TCR) therapy, where researchers can re-educate a patient’s own immune cells to kill the cancer. Professors Hans Stauss and Emma Morris are leading this project, which will develop treatments that selectively attack AML cells while avoiding damage to healthy tissues.

We are funding numerous clinical trials at UCL, including the BUBBLE TAP trial, which is being led by Professor Kwee Yong, which is testing a treatment for people whose myeloma has come back or treatment has stopped working.

Outside of TAP, we are also supporting a programme of clinical trials that hope to deliver improvements for people living with lymphoma. Dr Karl Peggs is leading the COBALT trial, which is looking to see if a new CAR-T therapy can help treat people with diffuse large B-cell lymphoma (DLBCL). This is the first time this type of treatment has been used for this type of lymphoma. The HOVON 127 BL trial is being led by Dr Andrew McMillan, which wants to see if we can reduce the side effects of chemotherapy in people with Burkitt lymphoma. Another trial called EuroNet-PHL-C2 is being led by Dr Stephen Daw, and is looking at reducing the side effects of radiotherapy in children and young people with Hodgkin lymphoma.

Some people with blood cancers, such as leukaemia, lymphoma or myeloma have a stem cell or bone marrow transplant using cells taken from their brother or sister. This is called a sibling allogeneic transplant. They often have lower doses of chemotherapy so it is sometimes called a mini (or reduced intensity) transplant. Professor Ronjon Chakraverty is running the ProT4 trial, which wants to see if giving extra T cells after a mini transplant can boost the success of the procedure, and the prevent blood cancer returning.

University of Cambridge

Research at The University of Cambridge has a number of projects that want to improve the outlook for people living with lymphoma. But we are also finding ways to treat acute myeloid leukaemia (AML) and are exploring the complex biology of myeloproliferative neoplasms (MPNs), which could lead to new treatments.

Burkitt lymphoma is an extremely aggressive form of non-Hodgkin lymphoma, and treatment usually involves high intensity chemotherapy. Although this can help many people, some cannot tolerate this treatment as they are too frail, and this intensive approach may leave younger people with devastating life-long treatment effects. Dr Daniel Hodson is focusing on finding new targeted treatment approaches, which could offer kinder and more effective treatment than conventional chemotherapy. Dr Hodson and his team are looking at a mutation in a gene called DDX3X that is found in one in three people with Burkitt lymphoma. Researchers want to see if drugs that specifically target this mutation could be a new treatment option that has less side effects than conventional chemotherapy.

Dr Martin Turner at the University of Cambridge is working closely with Professor Anne Willis from the MRC Toxicology Unit in Leicester to find new treatment avenues for people with non-Hodgkin lymphoma (NHL). The team have already found that in diffuse large B-cell lymphoma (DLBCL) there is an increase in the levels of a protein called eIF4B, and this increase is associated with a poorer outcome and can lead to resistance to chemotherapy. They now want to test new ways to inhibit eIF4B, which could lead to new treatment options for people with DLBCL that do not respond to current treatments.

We are also funding a project that is looking at splenic marginal zone lymphoma (SMZL) - a rare lymphoma that is found in the spleen. This type of lymphoma has a very variable clinical outcome, and at the moment, doctors are unable to predict the outcome of people with this disease. Professor Ming-Qing Du and his team will be exploring a genetic change in the KLF2 gene, which has been found in SMZL. He will investigate how these changes influence SMZL development, and aims to use this information to develop new treatment strategies. Professor Du is also leading a trial to find new therapeutic strategies for people with diffuse large B-cell lymphoma (DLBCL) who have not responded, or have become resistant to standard treatments.

We are supporting a project that is searching for new treatments for leukaemia, with a focus on AML. One of the commonest causes of leukaemia is the mutation of a class of genes called transcription factors. Transcription factors control the activity of many other genes, and operate in networks. Professor Bertie Gottgens and his team are comparing transcriptional networks in normal blood cells and AML cells. They aim to identify features specific to leukaemia cells that may be exploited for the development of new therapies that specifically target leukaemia cells.

Professor Anthony Green and his team are focussing on understanding the complex biology of myeloproliferative neoplasms (MPNs). The team will identify new genetic changes that happen in MPN. We also want to explore how these gene changes vary between people, and what influences this variation. This research will improve the way people with MPN are diagnosed, managed, and could lead to new treatments for the disease.

University of Oxford

Research at The University of Oxford is finding how acute myeloid leukaemia (AML) develops in children with Down Syndrome, and is trialling a new biological therapy in AML. We are also looking at new ways to target diffuse large B-cell lymphoma (DLBCL) that doesn’t respond to current chemotherapy. Two Trials Acceleration Programme (TAP) lymphoma clinical trials are being run from the Churchill Hospital – both are testing new treatments for people with peripheral T-cell lymphoma (PTCL) and diffuse B cell lymphoma (DLBCL) who are not responding to standard treatment, or have relapsed. We also have a TAP trial that wants to improve treatments for people with myelodysplastic syndrome (MDS). New treatments for leukaemia are also a focus, and we have a project that wants to understand the biology of infant acute lymphoblastic leukaemia (ALL) that could lead to much needed improvements in this rare and aggressive leukaemia. And we are also finding out what causes monoclonal gammopathy of undetermined significance (MGUS) to transform into myeloma.

Proteins called transcription factors have an important role in a wide range of blood cancers because they can bind to DNA and change the activity of many different genes. In diffuse large B-cell lymphoma (DLBCL) that doesn’t respond to current chemotherapy, levels of a transcription factor called FOXP1 are high. Gene pathways that are regulated by FOXP1 suggest that it helps cancer cells hide from the killing power of the immune system. Professor Alison Banham and her team want to know the role of the FOXP1 and FOXP2 transcription factors in DLBCL, and will investigate ways to target these proteins.

We are also supporting two lymphoma TAP trials - RomiCar and TORCH, both are being led by Dr Graham Collins. People with peripheral T-cell lymphoma (PTCL) are usually treated with chemotherapy, but sometimes this treatment fails to work, or the lymphoma may come back. The RomiCar study wants to know if combining romidepsin - a HDAC inhibitor that inhibits enzymes that cells need to grow and divide - and carfilzomib - a proteasome inhibitor that stops cancer cell growth - could help people with peripheral T-cell lymphoma (PTCL). Dr Collins will be looking at people with PTCL that has come back after treatment, or standard treatment has stopped working for them. The TORCH trial is testing a new biological therapy called vistusertib, which blocks the signals that cancer cells need to grow and divide. Vistusertib will be given to people with diffuse B cell lymphoma (DLBCL) that has continued to grow during standard treatment of chemotherapy and rituximab, or has come back afterwards.

Professor Terence Rabbitts and his team are looking at three proteins called LMO2, RAS and MLL, which interact with each other to cause leukaemia. The researchers want to develop small antibody fragments that can block the specific protein interactions, which could in the future lead to a new treatment options for people with leukaemia.

Our AML projects are being led by Professor Paresh Vyas. He is working with Professor Irene Roberts to study how AML develops in children with Down Syndrome. These children have an extra copy of chromosome 21 and have an increased risk of developing AML. They want to find out how chromosome 21 affects blood cell production in the womb, and what genetic events are important for leukaemia to form. This work hopes to improve the diagnosis and management of blood problems in babies with Down Syndrome, and could even help to prevent AML developing later on.

Professor Vyas is also leading the CAMELLIA trial. Researchers have found that AML cells have a large amount of a protein called CD47. This protein can protect the cancer cells by preventing the body’s immune system removing and destroying them. Hu5F9-G4 is a type of biological therapy called a monoclonal antibody. It works by blocking the signals of CD47 that protect the AML cells. Early studies have shown that Hu5F9-G4 can successfully eliminate AML cells in laboratory experiments, so researchers now want to see if Hu5F9-G4 can help treat people with AML.

We are also supporting a project that wants to find out what causes infant leukaemia. This type of is biologically different to childhood ALL, and is rare and aggressive. It develops in babies under 12 months of age, and still has very poor survival rates. The chemotherapy needed is gruelling—some babies die from the side effects of their treatment and many survivors suffer health problems in later life. Dr Anindita Roy wants to understand the origins of infant leukaemia, so she can design new therapies that target the specific genetic faults and networks that drive the disease.

Professor Claire Edwards is leading two myeloma projects. Multiple myeloma is nearly always preceded by the non-cancerous blood cell disorder termed monoclonal gammopathy of undetermined significance (MGUS). But not all people with MGUS will develop myeloma, and the reasons why only some people progress is still not fully understood. Professor Edwards has identified that low levels of a hormone called adiponectin is associated with progression from MGUS to myeloma. She aims to find out why this is, and if levels of adiponectin can flag people with MGUS who are at greatest risk in developing myeloma. Other molecules could be influencing this progression, such as levels of cholesterol, so Professor Edwards and her team will be looking at these other factors. By knowing what drives the progression of myeloma, doctors may be able to intervene to stop the cancer from happening in the first place.

We are also supporting the ELASTIC trial, which is being led by Dr Alexander Sternberg. Azacitidine – a type of chemotherapy – has been shown in a recent trial to improve survival in people with MDS. But many people in this trial had to stop or reduce treatment, because azacitidine caused low platelet counts and bleeding. The ELASTIC trial wants to see if adding a drug called eltrombopag helps to keep the platelet count up during azacitidine treatment.

University of Sussex

We are supporting one project at the University of Sussex, which is being led by Professor Michelle West.

Epstein-Barr virus infects white blood cells (B cells) and drives the development of many blood cancers in adults and children including Burkitt and Hodgkin lymphomas. But the role played by the virus in the development of these cancers however is still unclear. The team want to understand how some of the most important genes and pathways in lymphoma development are controlled by the Epstein-Barr virus, and investigate ways in which this can be disrupted by newly-developed drugs.